Krishna V. Komanduri, MD: So, I want to actually move on now to another disease. Steve, I’m going to turn to you because this is really at the heart of your practice. Can we talk now about diffuse large B-cell lymphoma? Of course, just in October, we had the approval of the second product, axi-cel, from KTE. And let’s place this in the context, first, of the need for salvage therapies in patients with relapsed or refractory non-Hodgkin’s lymphoma. Where are we and what are the outcomes for those patients?

Stephen J. Schuster, MD: I think as David said, and broadly speaking, probably our current therapies prior to the introduction of CAR T-cells were successful in about half of patients, and in the other half, we need something else. Certainly, since the advent of immunochemotherapy, adding anti-CD20 rituximab to chemotherapy, patients who are on clinical trials have about a two-thirds success rate, long-term remissions. However, in the real word the data look probably 50% or so. So, the other 50% needs something else. Although we’ve done somewhat better in the rituximab era, with primary therapy, our ability to salvage people using high-dose chemotherapy at transplant has become much worse.

Prior to the introduction of rituximab, depending on the responsiveness of patients’ relapsed disease, patients were responding to salvage therapies. You could probably say one-third or even higher of those patients with high-dose chemotherapy and autologous stem cell transplant. Well the data suggest now in the Rituxan era that the percentages are much lower. And certainly, patients who progress within a year of having rituximab chemotherapy induction have a dismal outcome with autotransplant and were an unmet need until the development of CAR T cells.

Now that’s not to say that CAR T cells is 100% effective in these patients, but the trials that are out there showing that there are durable remissions—in such bad prognosis patients who have either relapsed early after therapy or relapsed after transplant and have had refractory relapses—probably between 30% and 40% of patients can achieve durable long-term remission. So, this is a game changer. We’re going to be able to save the lives of patients who, just a few years ago, we couldn’t.

Krishna V. Komanduri, MD: I want to comment as a transplanter, but I actually agree with all of your conclusions. I do think that the efficacy of transplant in the post-Rituxan era is probably lower than it was before, that’s true. I do want to point out though in the early transplant era, we were transplanting patients really only after the age of 60 or 65 with autotransplant with 5% to 10% early mortality. We are, in most centers now, routinely doing autotransplants in patients up to the age of 75 with really close to 0% mortality. But I completely agree with you. I think that there are now some trials that are under design where patients who have relapsed, not who are refractory yet at the time of relapse, will actually be randomized to CAR T-cell therapy upfront versus our traditional, still standard-of-care approach of salvage therapy if chemotherapy sensitive in autotransplant.

Stephen J. Schuster, MD: Yes. There will be several such studies in 2018 that start, and I’m happy to say that all of them have a crossover. If you end up on the standard of care arm, which generally involved the salvage chemotherapy or the transplant, if that’s failing, you’ll have a T-cell product that you can crossover to. So, I think that’s good news.

Krishna V. Komanduri, MD: So, I think as a T-cell immunologist and a transplanter, I’m certainly happy to see transplant go away for certain subsets of our patients, but I think we also need the data and we need to do that in really perspective trials, and I’m glad that those trials are going to happen. And however they turn out, as long as it’s better for patients, I think that’s a good thing.

Transcript Edited for Clarity

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Transcript:

Krishna V. Komanduri, MD: So, I want to actually move on now to another disease. Steve, I’m going to turn to you because this is really at the heart of your practice. Can we talk now about diffuse large B-cell lymphoma? Of course, just in October, we had the approval of the second product, axi-cel, from KTE. And let’s place this in the context, first, of the need for salvage therapies in patients with relapsed or refractory non-Hodgkin’s lymphoma. Where are we and what are the outcomes for those patients?

Stephen J. Schuster, MD: I think as David said, and broadly speaking, probably our current therapies prior to the introduction of CAR T-cells were successful in about half of patients, and in the other half, we need something else. Certainly, since the advent of immunochemotherapy, adding anti-CD20 rituximab to chemotherapy, patients who are on clinical trials have about a two-thirds success rate, long-term remissions. However, in the real word the data look probably 50% or so. So, the other 50% needs something else. Although we’ve done somewhat better in the rituximab era, with primary therapy, our ability to salvage people using high-dose chemotherapy at transplant has become much worse.

Prior to the introduction of rituximab, depending on the responsiveness of patients’ relapsed disease, patients were responding to salvage therapies. You could probably say one-third or even higher of those patients with high-dose chemotherapy and autologous stem cell transplant. Well the data suggest now in the Rituxan era that the percentages are much lower. And certainly, patients who progress within a year of having rituximab chemotherapy induction have a dismal outcome with autotransplant and were an unmet need until the development of CAR T cells.

Now that’s not to say that CAR T cells is 100% effective in these patients, but the trials that are out there showing that there are durable remissions—in such bad prognosis patients who have either relapsed early after therapy or relapsed after transplant and have had refractory relapses—probably between 30% and 40% of patients can achieve durable long-term remission. So, this is a game changer. We’re going to be able to save the lives of patients who, just a few years ago, we couldn’t.

Krishna V. Komanduri, MD: I want to comment as a transplanter, but I actually agree with all of your conclusions. I do think that the efficacy of transplant in the post-Rituxan era is probably lower than it was before, that’s true. I do want to point out though in the early transplant era, we were transplanting patients really only after the age of 60 or 65 with autotransplant with 5% to 10% early mortality. We are, in most centers now, routinely doing autotransplants in patients up to the age of 75 with really close to 0% mortality. But I completely agree with you. I think that there are now some trials that are under design where patients who have relapsed, not who are refractory yet at the time of relapse, will actually be randomized to CAR T-cell therapy upfront versus our traditional, still standard-of-care approach of salvage therapy if chemotherapy sensitive in autotransplant.

Stephen J. Schuster, MD: Yes. There will be several such studies in 2018 that start, and I’m happy to say that all of them have a crossover. If you end up on the standard of care arm, which generally involved the salvage chemotherapy or the transplant, if that’s failing, you’ll have a T-cell product that you can crossover to. So, I think that’s good news.

Krishna V. Komanduri, MD: So, I think as a T-cell immunologist and a transplanter, I’m certainly happy to see transplant go away for certain subsets of our patients, but I think we also need the data and we need to do that in really perspective trials, and I’m glad that those trials are going to happen. And however they turn out, as long as it’s better for patients, I think that’s a good thing.